Given that the SLF and similar association tracts myelinate into late adolescence (Sowell et al., 1999), early MJ+ALC use may interfere with neuromaturation. The influence of CB-1 receptors on oligodendroglial development (Rodriguez de Fonseca et al., 1993) suggests that cannabis may impact cell differentiation and migratory processes. Poor differentiation of oligodendrocytes or death of oligodendroglia can lead to reductions in myelin initiation, deposition, compaction, and maintenance (Davis et al., 2003). Although cannabis can prevent oligodendrocyte death (Molina-Holgado et al., 2002b), early or chronic cannabis exposure may cause a down-regulation of CB-1 receptors and suppress oligodendrocyte function during neurodevelopment. Cannabis-induced alterations in myelin proteolipid protein could also affect the expression of this gene, particularly with long-term exposure (Grigorenko et al., 2002). Down-regulation of myelin-related genes (Lewohl et al., 2000; Mayfield et al., 2002) and deficits in oligodendrocyte myelin glycoprotein (Okamoto et al., 2006) found in chronic alcoholism may further interact with altered processes associated with cannabis exposure. Focal areas of fiber disintegrity, as suggested by the current study, may result from any of these neurodevelopmental processes.
